Tamoxifen exerts direct and microglia-mediated effects preventing neuroinflammatory changes in the adult mouse hippocampal neurogenic niche.

Autor: Crisci I; Department of Life Sciences and Systems Biology, University of Turin, Turin, Italy.; NICO-Neuroscience Institute Cavalieri Ottolenghi, University of Turin, Orbassano, Italy.; Institut de Génétique et de Biologie Moléculaire et Cellulaire, INSERM U1258, CNRS UMR 7104, Université de Strasbourg, Illkirch, France., Bonzano S; Department of Life Sciences and Systems Biology, University of Turin, Turin, Italy.; NICO-Neuroscience Institute Cavalieri Ottolenghi, University of Turin, Orbassano, Italy., Nicolas Z; Institut de Génétique et de Biologie Moléculaire et Cellulaire, INSERM U1258, CNRS UMR 7104, Université de Strasbourg, Illkirch, France., Dallorto E; Department of Life Sciences and Systems Biology, University of Turin, Turin, Italy.; NICO-Neuroscience Institute Cavalieri Ottolenghi, University of Turin, Orbassano, Italy., Peretto P; Department of Life Sciences and Systems Biology, University of Turin, Turin, Italy.; NICO-Neuroscience Institute Cavalieri Ottolenghi, University of Turin, Orbassano, Italy., Krezel W; Institut de Génétique et de Biologie Moléculaire et Cellulaire, INSERM U1258, CNRS UMR 7104, Université de Strasbourg, Illkirch, France., De Marchis S; Department of Life Sciences and Systems Biology, University of Turin, Turin, Italy.; NICO-Neuroscience Institute Cavalieri Ottolenghi, University of Turin, Orbassano, Italy.
Jazyk: angličtina
Zdroj: Glia [Glia] 2024 Jul; Vol. 72 (7), pp. 1273-1289. Date of Electronic Publication: 2024 Mar 21.
DOI: 10.1002/glia.24526
Abstrakt: Tamoxifen-inducible systems are widely used in research to control Cre-mediated gene deletion in genetically modified animals. Beyond Cre activation, tamoxifen also exerts off-target effects, whose consequences are still poorly addressed. Here, we investigated the impact of tamoxifen on lipopolysaccharide (LPS)-induced neuroinflammatory responses, focusing on the neurogenic activity in the adult mouse dentate gyrus. We demonstrated that a four-day LPS treatment led to an increase in microglia, astrocytes and radial glial cells with concomitant reduction of newborn neurons. These effects were counteracted by a two-day tamoxifen pre-treatment. Through selective microglia depletion, we elucidated that both LPS and tamoxifen influenced astrogliogenesis via microglia mediated mechanisms, while the effects on neurogenesis persisted even in a microglia-depleted environment. Notably, changes in radial glial cells resulted from a combination of microglia-dependent and -independent mechanisms. Overall, our data reveal that tamoxifen treatment per se does not alter the balance between adult neurogenesis and astrogliogenesis but does modulate cellular responses to inflammatory stimuli exerting a protective role within the adult hippocampal neurogenic niche.
(© 2024 Wiley Periodicals LLC.)
Databáze: MEDLINE
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